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IMPORTANCE: Socioeconomically disadvantaged individuals (ie, those with low socioeconomic status [SES]) have difficulty quitting smoking and may benefit from incentive-based cessation interventions. OBJECTIVES: To evaluate the impact of incentivizing smoking abstinence on smoking cessation among adults with low SES. DESIGN, SETTING, AND PARTICIPANTS: This study used a 2-group randomized clinical trial design. Data collection occurred between January 30, 2017, and February 7, 2022. Participants included adults with low SES who were willing to undergo smoking cessation treatment. Data were analyzed from April 18, 2023, to April 19, 2024. INTERVENTIONS: Participants were randomized to usual care (UC) for smoking cessation (counseling plus pharmacotherapy) or UC plus abstinence-contingent financial incentives (UC plus FI). MAIN OUTCOMES AND MEASURES: The primary outcome was biochemically verified 7-day point prevalence smoking abstinence (PPA) at 26 weeks after the quit date. Secondary outcomes included biochemically verified 7-day PPA at earlier follow-ups, 30-day PPA at 12 and 26 weeks, repeated 7-day PPA, and continuous abstinence. Multiple approaches were employed to handle missing outcomes at follow-up, including categorizing missing data as smoking (primary), complete case analysis, and multiple imputation. RESULTS: The 320 participants had a mean (SD) age of 48.9 (11.6) and were predominantly female (202 [63.1%]); 82 (25.6%) were Black, 15 (4.7%) were Hispanic, and 200 (62.5%) were White; and 146 (45.6%) participated during the COVID-19 pandemic. Overall, 161 were randomized to UC and 159 were randomized to UC plus FI. After covariate adjustment with missing data treated as smoking, assignment to UC plus FI was associated with a greater likelihood of 7-day PPA at the 4-week (adjusted odds ratio [AOR], 3.11 [95% CI, 1.81-5.34]), 8-week (AOR, 2.93 [95% CI, 1.62-5.31]), and 12-week (AOR, 3.18 [95% CI, 1.70-5.95]) follow-ups, but not at the 26-week follow-up (22 [13.

n/a, Funding Agencies|Barncancerfonden (Swedish Childhood Cancer Foundation); Transgenic Facility at Lund University; Swedish Pediatric Leukemia Foundation; Swedish Cancer Foundation; Swedish Research Council; Knut and Alice Wallenberg Foundation

Aktuelle In-vivo-Methoden zur Bewertung der Belastung und Dehnung der Achillessehne (AT) in der biomechanischen Literatur haben bestimmte Einschränkungen, die sorgfältig berücksichtigt werden müssen. Daher hatte die erste Studie zum Ziel, die AT-Dehnung und -Kraft während der Fortbewegung mithilfe einer genauen, nicht-invasiven Methode zu messen. Die Länge der AT wurde unter Berücksichtigung ihrer Krümmung mit reflektierenden Folienmarkern von der Insertion am Fersenbein bis zum Übergang zwischen der Muskel-Sehnen-Verbindung des Musculus gastrocnemius medialis (GM-MTJ) gemessen. Die Kraft der AT wurde durch Anpassung einer quadratischen Funktion an die experimentelle Kraft-Längen-Kurve der Sehne ermittelt, die aus maximalen freiwilligen isometrischen Kontraktionen (MVC) gewonnen wurde. Die Ergebnisse der zweiten Studie zeigen, dass eine Erhöhung der Gehgeschwindigkeit zu einer 21%igen Abnahme der maximalen AT-Kraft bei höheren Geschwindigkeiten im Vergleich zur bevorzugten Geschwindigkeit führt, während die Nettobelastung der AT-Kraft am Sprunggelenk (ATF-Arbeit) in Abhängigkeit von der Gehgeschwindigkeit zunimmt. Darüber hinaus trugen eine frühere Plantarflexion, erhöhte elektromyografische Aktivität der Muskeln Sol und GM sowie der Energieübertrag von Knie- zu Sprunggelenk durch die biartikulären Musculi gastrocnemii zu einer 1,7- bzw. 2,4-fachen Zunahme der netto ATF-Mechanik-Arbeit bei Übergangs- und maximalen Gehgeschwindigkeiten bei. Das Ziel der dritten Studie war es, die in der ersten Studie vorgeschlagene Methode zu vereinfachen, indem die Anzahl der reflektierenden Folienmarker reduziert wurde, jedoch die hohe Genauigkeit beibehalten wurde. Die Krümmung der AT wurde mithilfe von reflektierenden Folienmarkern zwischen dem Ursprung des GM-MTJ und dem Einführungsmarker am Fersenbein beurteilt. Unsere Ergebnisse zeigen, dass eine Reduzierung der Anzahl der Folienmarker um 70% beim Gehen und um 50% beim Laufen zu einem marginalen Fehler führen würde und somit e, Current in vivo methods to assess the Achilles tendon (AT) strain and loading in the biomechanics literature have certain limitations that require careful consideration. Therefore, the first study was to measure the AT strain and quantify AT force during locomotion with an accurate non-invasive method. AT length was measured considering its curvature using reflective foil markers from AT insertion at calcaneus to gastrocnemius medialis muscle-tendon junction (GM-MTJ). The force of the AT was calculated by fitting a quadratic function to the experimental tendon force-length curve obtained from maximum voluntary isometric contractions (MVC). The findings in second study indicate that an increase in walking speed leads to a 21% decrease in maximum AT force at higher speeds compared to the preferred speed, yet the net work of the AT force at the ankle joint (ATF-work) increased as a function of walking speed. Additionally, an earlier plantar flexion, increased electromyographic activity of the Sol and GM muscles, and knee-to-ankle joint energy transfer via the biarticular gastrocnemii contributed to a 1.7 and 2.4-fold increase in the net ATF-mechanical work in the transition and maximum walking speeds. The objective of the third study was to simplify the proposed method in the first study by reducing the number of foil reflective markers while preserving high accuracy. The AT curvature was assessed using reflective foil markers between the GM-MTJ origin and the calcaneal insertion marker. Our results indicate that reducing the number of foil markers by 70% during walking and 50% during running would result in a marginal error and, thus, a negligible effect on the AT length and maximum strain measurement.

Increasing walking speed is accompanied by an increase of the mechanical power and work performed at the ankle joint despite the decrease of the intrinsic muscle force potential of the soleus (Sol) and gastrocnemius medialis (GM) muscles. In the present study, we measured Achilles tendon (AT) elongation and, based on an experimentally determined AT force–elongation relationship, quantified AT force at four walking speeds (slow 0.7 m.s−1, preferred 1.4 m.s−1, transition 2.0 m.s−1, and maximum 2.6 ± 0.3 m.s−1). Further, we investigated the mechanical power and work of the AT force at the ankle joint and, separately, the mechanical power and work of the monoarticular Sol at the ankle joint and the biarticular gastrocnemii at the ankle and knee joints. We found a 21% decrease in maximum AT force at the two higher speeds compared to the preferred; however, the net work of the AT force at the ankle joint (ATF work) increased as a function of walking speed. An earlier plantar flexion accompanied by an increased electromyographic activity of the Sol and GM muscles and a knee-to-ankle joint energy transfer via the biarticular gastrocnemii increased the net ATF mechanical work by 1.7 and 2.4-fold in the transition and maximum walking speed, respectively. Our findings provide first-time evidence for a different mechanistic participation of the monoarticular Sol muscle (i.e., increased contractile net work carried out) and the biarticular gastrocnemii (i.e., increased contribution of biarticular mechanisms) to the speed-related increase of net ATF work., Peer Reviewed

Natural killer (NK) cells play roles in viral clearance and early surveillance against malignant transformation, yet our knowledge of the underlying mechanisms controlling their development and functions remain incomplete. To reveal cell fate-determining pathways in NK cell progenitors (NKP), we utilized an unbiased approach and generated comprehensive gene expression profiles of NK cell progenitors. We found that the NK cell program was gradually established in the CLP to preNKP and preNKP to rNKP transitions. In line with FOXO1 and FOXO3 being co-expressed through the NK developmental trajectory, the loss of both perturbed the establishment of the NK cell program and caused stalling in both NK cell development and maturation. In addition, we found that the combined loss of FOXO1 and FOXO3 caused specific changes to the composition of the non-cytotoxic innate lymphoid cell (ILC) subsets in bone marrow, spleen, and thymus. By combining transcriptome and chromatin profiling, we revealed that FOXO TFs ensure proper NK cell development at various lineage-commitment stages through orchestrating distinct molecular mechanisms. Combined FOXO1 and FOXO3 deficiency in common and innate lymphoid cell progenitors resulted in reduced expression of genes associated with NK cell development including ETS-1 and their downstream target genes. Lastly, we found that FOXO1 and FOXO3 controlled the survival of committed NK cells via gene regulation of IL-15R beta (CD122) on rNKPs and bone marrow NK cells. Overall, we revealed that FOXO1 and FOXO3 function in a coordinated manner to regulate essential developmental genes at multiple stages during murine NK cell and ILC lineage commitment.

The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs.

Natural killer (NK) cells play roles in viral clearance and early surveillance against malignant transformation, yet our knowledge of the underlying mechanisms controlling their development and functions remain incomplete. To reveal cell fate-determining pathways in NK cell progenitors (NKP), we utilized an unbiased approach and generated comprehensive gene expression profiles of NK cell progenitors. We found that the NK cell program was gradually established in the CLP to preNKP and preNKP to rNKP transitions. In line with FOXO1 and FOXO3 being co-expressed through the NK developmental trajectory, the loss of both perturbed the establishment of the NK cell program and caused stalling in both NK cell development and maturation. In addition, we found that the combined loss of FOXO1 and FOXO3 caused specific changes to the composition of the non-cytotoxic innate lymphoid cell (ILC) subsets in bone marrow, spleen, and thymus. By combining transcriptome and chromatin profiling, we revealed that FOXO TFs ensure proper NK cell development at various lineage-commitment stages through orchestrating distinct molecular mechanisms. Combined FOXO1 and FOXO3 deficiency in common and innate lymphoid cell progenitors resulted in reduced expression of genes associated with NK cell development including ETS-1 and their downstream target genes. Lastly, we found that FOXO1 and FOXO3 controlled the survival of committed NK cells via gene regulation of IL-15R beta (CD122) on rNKPs and bone marrow NK cells. Overall, we revealed that FOXO1 and FOXO3 function in a coordinated manner to regulate essential developmental genes at multiple stages during murine NK cell and ILC lineage commitment.

The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs.

Natural killer (NK) cells play roles in viral clearance and early surveillance against malignant transformation, yet our knowledge of the underlying mechanisms controlling their development and functions remain incomplete. To reveal cell fate-determining pathways in NK cell progenitors (NKP), we utilized an unbiased approach and generated comprehensive gene expression profiles of NK cell progenitors. We found that the NK cell program was gradually established in the CLP to preNKP and preNKP to rNKP transitions. In line with FOXO1 and FOXO3 being co-expressed through the NK developmental trajectory, the loss of both perturbed the establishment of the NK cell program and caused stalling in both NK cell development and maturation. In addition, we found that the combined loss of FOXO1 and FOXO3 caused specific changes to the composition of the non-cytotoxic innate lymphoid cell (ILC) subsets in bone marrow, spleen, and thymus. By combining transcriptome and chromatin profiling, we revealed that FOXO TFs ensure proper NK cell development at various lineage-commitment stages through orchestrating distinct molecular mechanisms. Combined FOXO1 and FOXO3 deficiency in common and innate lymphoid cell progenitors resulted in reduced expression of genes associated with NK cell development including ETS-1 and their downstream target genes. Lastly, we found that FOXO1 and FOXO3 controlled the survival of committed NK cells via gene regulation of IL-15R beta (CD122) on rNKPs and bone marrow NK cells. Overall, we revealed that FOXO1 and FOXO3 function in a coordinated manner to regulate essential developmental genes at multiple stages during murine NK cell and ILC lineage commitment.

The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs.

Natural killer (NK) cells play roles in viral clearance and early surveillance against malignant transformation, yet our knowledge of the underlying mechanisms controlling their development and functions remain incomplete. To reveal cell fate-determining pathways in NK cell progenitors (NKP), we utilized an unbiased approach and generated comprehensive gene expression profiles of NK cell progenitors. We found that the NK cell program was gradually established in the CLP to preNKP and preNKP to rNKP transitions. In line with FOXO1 and FOXO3 being co-expressed through the NK developmental trajectory, the loss of both perturbed the establishment of the NK cell program and caused stalling in both NK cell development and maturation. In addition, we found that the combined loss of FOXO1 and FOXO3 caused specific changes to the composition of the non-cytotoxic innate lymphoid cell (ILC) subsets in bone marrow, spleen, and thymus. By combining transcriptome and chromatin profiling, we revealed that FOXO TFs ensure proper NK cell development at various lineage-commitment stages through orchestrating distinct molecular mechanisms. Combined FOXO1 and FOXO3 deficiency in common and innate lymphoid cell progenitors resulted in reduced expression of genes associated with NK cell development including ETS-1 and their downstream target genes. Lastly, we found that FOXO1 and FOXO3 controlled the survival of committed NK cells via gene regulation of IL-15R beta (CD122) on rNKPs and bone marrow NK cells. Overall, we revealed that FOXO1 and FOXO3 function in a coordinated manner to regulate essential developmental genes at multiple stages during murine NK cell and ILC lineage commitment.

The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs.

Natural killer (NK) cells play roles in viral clearance and early surveillance against malignant transformation, yet our knowledge of the underlying mechanisms controlling their development and functions remain incomplete. To reveal cell fate-determining pathways in NK cell progenitors (NKP), we utilized an unbiased approach and generated comprehensive gene expression profiles of NK cell progenitors. We found that the NK cell program was gradually established in the CLP to preNKP and preNKP to rNKP transitions. In line with FOXO1 and FOXO3 being co-expressed through the NK developmental trajectory, the loss of both perturbed the establishment of the NK cell program and caused stalling in both NK cell development and maturation. In addition, we found that the combined loss of FOXO1 and FOXO3 caused specific changes to the composition of the non-cytotoxic innate lymphoid cell (ILC) subsets in bone marrow, spleen, and thymus. By combining transcriptome and chromatin profiling, we revealed that FOXO TFs ensure proper NK cell development at various lineage-commitment stages through orchestrating distinct molecular mechanisms. Combined FOXO1 and FOXO3 deficiency in common and innate lymphoid cell progenitors resulted in reduced expression of genes associated with NK cell development including ETS-1 and their downstream target genes. Lastly, we found that FOXO1 and FOXO3 controlled the survival of committed NK cells via gene regulation of IL-15R beta (CD122) on rNKPs and bone marrow NK cells. Overall, we revealed that FOXO1 and FOXO3 function in a coordinated manner to regulate essential developmental genes at multiple stages during murine NK cell and ILC lineage commitment.

The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs.

The purpose of the current study was to assess in vivo Achilles tendon (AT) mechanical loading and strain energy during locomotion. We measured AT length considering its curve-path shape. Eleven participants walked at 1.4 m/s and ran at 2.5 m/s and 3.5 m/s on a treadmill. The AT length was defined as the distance between its origin at the gastrocnemius medialis myotendinous junction (MTJ) and the calcaneal insertion. The MTJ was tracked using ultrasonography and projected to the reconstructed skin surface to account for its misalignment. Skin-to-bone displacements were assessed during a passive rotation (5°/s) of the ankle joint. Force and strain energy of the AT during locomotion were calculated by fitting a quadratic function to the experimentally measured tendon force–length curve obtained from maximum voluntary isometric contractions. The maximum AT strain and force were affected by speed (p < 0.05, ranging from 4.0 to 4.9% strain and 1.989 to 2.556 kN), yet insufficient in magnitude to be considered as an effective stimulus for tendon adaptation. Besides the important tendon energy recoil during the propulsion phase (7.8 to 11.3 J), we found a recoil of elastic strain energy at the beginning of the stance phase of running (70–77 ms after touch down) between 1.7 ± 0.6 and 1.9 ± 1.1 J, which might be functionally relevant for running efficiency., Peer Reviewed

This article was supported by the German Research Foundation (DFG) and the Open Access Publication Fund of Humboldt-Universität zu Berlin., The purpose of the current study was to assess in vivo Achilles tendon (AT) mechanical loading and strain energy during locomotion. We measured AT length considering its curve-path shape. Eleven participants walked at 1.4 m/s and ran at 2.5 m/s and 3.5 m/s on a treadmill. The AT length was defined as the distance between its origin at the gastrocnemius medialis myotendinous junction (MTJ) and the calcaneal insertion. The MTJ was tracked using ultrasonography and projected to the reconstructed skin surface to account for its misalignment. Skin-to-bone displacements were assessed during a passive rotation (5°/s) of the ankle joint. Force and strain energy of the AT during locomotion were calculated by fitting a quadratic function to the experimentally measured tendon force–length curve obtained from maximum voluntary isometric contractions. The maximum AT strain and force were affected by speed (p < 0.05, ranging from 4.0 to 4.9% strain and 1.989 to 2.556 kN), yet insufficient in magnitude to be considered as an effective stimulus for tendon adaptation. Besides the important tendon energy recoil during the propulsion phase (7.8 to 11.3 J), we found a recoil of elastic strain energy at the beginning of the stance phase of running (70–77 ms after touch down) between 1.7 ± 0.6 and 1.9 ± 1.1 J, which might be functionally relevant for running efficiency., Peer Reviewed

The consideration of the Achilles tendon (AT) curvature is crucial for the precise determination of AT length and strain. We previously established an ultrasound-kinematic-based method to quantify the curvature, using a line of reflective foil skin markers covering the AT from origin to insertion. The current study aimed to simplify the method by reducing the number of markers while maintaining high accuracy. Eleven participants walked (1.4 m/s) and ran (2.5, 3.5 m/s) on a treadmill, and the AT curvature was quantified using reflective foil markers aligned with the AT between the origin on the gastrocnemius myotendinous-junction (tracked by ultrasound) and a marker on the calcaneal insertion. Foil markers were then systematically removed, and the introduced error on the assessment of AT length and strain was calculated. We found a significant main effect of marker number on the measurement error of AT length and strain (p<0.001). Using more than 30% of the full marker-set for walking and 50% for running, the R2 of the AT length error saturated, corresponding to average errors of <0.1 mm and <0.15% strain. Therefore, a substantially reduced marker-set, associated with a marginal error, can be recommended for considering the AT curvature in the determination of AT length and strain., Peer Reviewed

We present qcor - a language extension to C++ and compiler implementation that enables heterogeneous quantum-classical programming, compilation, and execution in a single-source context. Our work provides a first-of-its-kind C++ compiler enabling high-level quantum kernel (function) expression in a quantum-language agnostic manner, as well as a hardware-agnostic, retargetable compiler workflow targeting a number of physical and virtual quantum computing backends. qcor leverages novel Clang plugin interfaces and builds upon the XACC system-level quantum programming framework to provide a state-of-the-art integration mechanism for quantum-classical compilation that leverages the best from the community at-large. qcor translates quantum kernels ultimately to the XACC intermediate representation, and provides user-extensible hooks for quantum compilation routines like circuit optimization, analysis, and placement. This work details the overall architecture and compiler workflow for qcor, and provides a number of illuminating programming examples demonstrating its utility for near-term variational tasks, quantum algorithm expression, and feed-forward error correction schemes.

In today’s society we buy, use and throw things away which has made waste an environmental problem which affects our planet negatively. To prevent further development of consumerism, sustainable movements must be made where society must climb up the ladder of waste hierarchy and start to integrate in preventing the production of waste. One way to manage and prevent waste is through changed consumer practices that encourage repair. As it seems the discussion about repair is a missing part in the Swedish structure about waste management. It is not a part of what children are being taugt and it is not a part of the ongoing discussion about environmental issues. The purpose with this thesis is to plant a seed of change among children and bring back the mindset where humanity integrate with the planet. The research question for this thesis is: “how can the value of repair be increased through resilience among children who are the future influencers?”. Through my research and methodology I decided to design a prototype of a pedagogical toolkit for kindergarten consisting of storytelling through a book and an interactive product. As a part of the design process, a workshop was performed where the core concept of my toolkit was tried out at a kindergarten. The workshop resulted in good management from the children of the content of the story and the interactive product. A pluralistic discussion about how they could help the main character Julia with the broken chair in relation to waste management occurred. The children were “nudged” through the story in the decisision making towards repair, which was the option they choosed. The prototype of my toolkit might not at this stage have resulted in actual increased knowledge about waste hierarchy and prevention of waste. However, according to my opinionen it has contribuited to an increased discussion about repair at the local place where I had my workshop. Hopefully the toolkit has started a thinking process in those children’s

In today’s society we buy, use and throw things away which has made waste an environmental problem which affects our planet negatively. To prevent further development of consumerism, sustainable movements must be made where society must climb up the ladder of waste hierarchy and start to integrate in preventing the production of waste. One way to manage and prevent waste is through changed consumer practices that encourage repair. As it seems the discussion about repair is a missing part in the Swedish structure about waste management. It is not a part of what children are being taugt and it is not a part of the ongoing discussion about environmental issues. The purpose with this thesis is to plant a seed of change among children and bring back the mindset where humanity integrate with the planet. The research question for this thesis is: “how can the value of repair be increased through resilience among children who are the future influencers?”. Through my research and methodology I decided to design a prototype of a pedagogical toolkit for kindergarten consisting of storytelling through a book and an interactive product. As a part of the design process, a workshop was performed where the core concept of my toolkit was tried out at a kindergarten. The workshop resulted in good management from the children of the content of the story and the interactive product. A pluralistic discussion about how they could help the main character Julia with the broken chair in relation to waste management occurred. The children were “nudged” through the story in the decisision making towards repair, which was the option they choosed. The prototype of my toolkit might not at this stage have resulted in actual increased knowledge about waste hierarchy and prevention of waste. However, according to my opinionen it has contribuited to an increased discussion about repair at the local place where I had my workshop. Hopefully the toolkit has started a thinking process in those children’s

BackgroundWe previously reported that functional recovery of rats with spinal cord contusions can occur after acute transplantation of neural stem cells distal to the site of injury. To investigate the effects of timing of administration of human neural stem cell (hNSC) distal to the site of spinal cord injury on functional outcomes in an animal model.MethodsThirty-six adult female Long-Evans hooded rats were randomized into three experimental and three control groups with six animals in each group. The T10 level was exposed via posterior laminectomy, and a moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor (MASCIS, W.M. Keck Center for Collaborative Neuroscience, Piscataway, NJ, USA). The animals received either an intrathecal injection of hNSCs or control media through a separate distal laminotomy immediately, one week or four weeks after the induced spinal cord injury. Observers were blinded to the interventions. Functional assessment was measured immediately after injury and weekly using the Basso, Beattie, Bresnahan (BBB) locomotor rating score.ResultsA statistically significant functional improvement was seen in all three time groups when compared to their controls (acute, mean 9.2 vs. 4.5, P=0.016; subacute, mean 11.1 vs. 6.8, P=0.042; chronic, mean 11.3 vs. 5.8, P=0.035). Although there was no significant difference in the final BBB scores comparing the groups that received hNSCs, the group which achieved the greatest improvement from the time of cell injection was the subacute group (+10.3) and was significantly greater than the chronic group (+5.1, P=0.02).ConclusionsThe distal intrathecal transplantation of hNSCs into the contused spinal cord of a rat led to significant functional recovery of the spinal cord when injected in the acute, subacute and chronic phases of spinal cord injury (SCI), although the greatest gains appeared to be in the subacute timing group.

In jawed vertebrates, development of an adaptive immune-system is essential for protection of the born organism against otherwise life-threatening pathogens. Myeloid cells of the innate immune system are formed early in development, whereas lymphopoiesis has been suggested to initiate much later, following emergence of definitive hematopoietic stem cells (HSCs). Herein, we demonstrate that the embryonic lymphoid commitment process initiates earlier than previously appreciated, prior to emergence of definitive HSCs, through establishment of a previously unrecognized entirely immune-restricted and lymphoid-primed progenitor. Notably, this immune-restricted progenitor appears to first emerge in the yolk sac and contributes physiologically to the establishment of lymphoid and some myeloid components of the immune-system, establishing the lymphomyeloid lineage restriction process as an early and physiologically important lineage-commitment step in mammalian hematopoiesis

Anthrax, a disease caused by the bacterium Bacillus Anthracis, poses a threat worldwide due to its debilitating symptoms and lethality. The toxins released by the bacteria (PA, LF, EF) enter cells, cause most symptoms and allow the bacterial growth. LF is a metalloprotease, which cleaves and inactivates MKK in humans, therefore inhibiting MAPK signaling in many cell types. EF is a potent adenylate cyclase and PA facilitates the entry of LF and EF into host cells. In addition to the classic antibiotic and vaccine therapies, one strategy to combat anthrax would be to introduce dominant negative toxins, which could antagonize the wild type toxins, and potentially save lives in the later stages of the disease when antibiotics can no longer prevent death. Model systems such as Drosophila Melanogaster, can be used to study the activity of anthrax and other bacterial toxins, and provide a way to screen such Dominant-negative alleles. We used the Novel OVerexpression Allele screening method to generate several LF alleles which exhibit dominant negative activity as revealed by wing phenotypes in flies. We then attempted to analyze the molecular lesion causing the novel activity of these mutants

Anthrax, a disease caused by the bacterium Bacillus Anthracis, poses a threat worldwide due to its debilitating symptoms and lethality. The toxins released by the bacteria (PA, LF, EF) enter cells, cause most symptoms and allow the bacterial growth. LF is a metalloprotease, which cleaves and inactivates MKK in humans, therefore inhibiting MAPK signaling in many cell types. EF is a potent adenylate cyclase and PA facilitates the entry of LF and EF into host cells. In addition to the classic antibiotic and vaccine therapies, one strategy to combat anthrax would be to introduce dominant negative toxins, which could antagonize the wild type toxins, and potentially save lives in the later stages of the disease when antibiotics can no longer prevent death. Model systems such as Drosophila Melanogaster, can be used to study the activity of anthrax and other bacterial toxins, and provide a way to screen such Dominant-negative alleles. We used the Novel OVerexpression Allele screening method to generate several LF alleles which exhibit dominant negative activity as revealed by wing phenotypes in flies. We then attempted to analyze the molecular lesion causing the novel activity of these mutants

X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency that results from mutations within the gene encoding Bruton's tyrosine kinase (BTK). Many XLA-associated mutations affect splicing of BTK pre-mRNA and severely impair B cell development. Here, we assessed the potential of antisense, splice-correcting oligonucleotides (SCOs) targeting mutated BTKtranscripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we engineered a transgenic mouse that harbors a BAC with an authentic, mutated, splice-defective human BTK gene. BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the orthologous mouse protein. Using this model, we determined that BTK-specific SCOs are able to correct aberrantly spliced BTK in B lymphocytes, including pro-B cells. Correction of BTK mRNA restored expression of functional protein, as shown both by enhanced lymphocyte survival and reestablished BTK activation upon B cell receptor stimulation. Furthermore, SCO treatment corrected splicing and restored BTK expression in primary cells from patients with XLA. Together, our data demonstrate that SCOs can restore BTK function and that BTK-targeting SCOs have potential as personalized medicine in patients with XLA., AuthorCount:21

In today’s competitive market, retaining existing customers is more profitable than attracting new ones. Customer Relation Management (CRM) is a strategic approach to keep and fulfill customers and push them to return to the company.Loyalty program is known as a useful tool to meet the goals of CRM. Based on the importance of customers in the hospitality industry loyalty program is a common strategy which is employed in different segment of this industry such as the hotel business. The purpose of this thesis was to gain a better understanding of the characteristics of loyalty programs in the Iranian hotel industry. To do a better implementation of this research we study customer loyalty program of Parsian complex which is run under the name of VIP club as a case study.For this thesis we developed the questionnaire with 38 questions which were filled by 60 managers of Parsian hotels and VIP program designers. The data suggested that VIP program will not interest any of the studied benefits; Strong database and financial benefits.The findings indicate that The VIP program faces with some challenges; Inappropriate rewards system, not well designed loyalty program structure and lack of goals clarification.Based on this study Parsian complex should clarify the goals of loyalty program and consider managers and customers’ view to design a strong loyalty program which can increase customer loyalty and employees’ support., Validerat; 20141110 (marikav)

Whether signals mediated via growth factor receptors (GFRs) might influence lineage fate in multipotent progenitors (MPPs) is unclear. We explored this issue in a mouse knockin model of gain-of-function Flt3-ITD mutation because FLT3-ITDs are paradoxically restricted to acute myeloid leukemia even though Flt3 primarily promotes lymphoid development during normal hematopoiesis. When expressed in MPPs, Flt3-ITD collaborated with Runx1 mutation to induce high-penetrance aggressive leukemias that were exclusively of the myeloid phenotype. Flt3-ITDs preferentially expanded MPPs with reduced lymphoid and increased myeloid transcriptional priming while compromising early B and T lymphopoiesis. Flt3-ITD-induced myeloid lineage bias involved upregulation of the transcription factor Pu.1, which is a direct target gene of Stat3, an aberrantly activated target of Flt3-ITDs, further establishing how lineage bias can be inflicted on MPPs through aberrant GFR signaling. Collectively, these findings provide new insights into how oncogenic mutations might subvert the normal process of lineage commitment and dictate the phenotype of resulting malignancies.

Triple-play services including video, voice and data demand service differentiation to provide end-users quality-of-service (QoS) requirements. Optical Code Division Multiple Access (OCMDA) systems have emerged as suitable solution to provide such QoS differentiation by varying the code weight. In this paper, the effect of choosing different code weight sets on the system capacity of a Variable-Weight OCDMA (VW-OCDMA) system deploying different detection techniques is investigated. Mathematical analysis is used to drive the Bit-Error Rate (BER) of active users in the system.

Multi-wavelength Optical Code Division Multiple Access (OCDMA) systems suffer from fiber impairments including non-linear effects (NLE), especially when the number of wavelengths and input power level increase. In this paper, a review of NLE, including self-phase modulation, cross-phase modulation, four wave mixing (FWM), stimulated Brillouin scattering and stimulated Raman scattering on the system performance of OCDMA systems is presented. As some of the non-linearities may have correlated effects on the performance of the system, the relations between these effects are also investigated. Bit error rate results reveal that the most important unwanted effect was caused by FWM.

Recently, Optical Code Division Multiple Access (OCDMA) systems are among the popular choice of research areas deployed in metro networks as they could provide service differentiation for different quality of signals in such networks. In OCDMA system Quality of Service (QoS) differentiation is realized by assigning dierent code weight or length for each user or service. In actual implementation which involves ber in the transmission, the ber impairment such as dispersion and nonlinear effects can greatly reduce the performance of the system, especially when the bit rate is high. In this thesis, mathematical and simulation model is proposed to analyze the performance of a Variable-Weight OCDMA (VW-OCDMA) system. The research was carried out by firstly developing a mathematical model for VWOCDMA system deploying Direct Detection (DD) and AND detection techniques. In the numerical analysis the effects of phase-induced intensity noise, shot noise and thermal noise was taken into account. Subsequently, different detection schemes i.e. DD and AND subtraction, as well as different optical sources i.e. broadband and laser were analyzed using software simulation. Three weights of 2, 4 and 6 were chosen for different services which represent voice, data and video. The simulationse tup was also used to investigate the effects of fiber impairments including chromatic dispersion, self-phase modulation and four wave mixing. Various dispersion compensation techniques were then applied in VW-OCDMA system. Finally,feasibility of the proposed system was investigated using practical experimentation to compare with the system’s performance in simulation environment. Three users with weight 6, 4 and 2 were used in experimental design, each transmitting data at rate of 1.25 Gbps. With reference to BER of 10−3, 10−9 and 10−12 for voice, data and video respectively, VW-OCDMA deploying DD scheme supports 95 users each operating at bit rate of 1.25 Gbps. Moreover, using non-zero dispersion s

Multi-wavelength Optical Code Division Multiple Access (OCDMA) systems suffer from fiber impairments including non-linear effects (NLE), especially when the number of wavelengths and input power level increase. In this paper, a review of NLE, including self-phase modulation, cross-phase modulation, four wave mixing (FWM), stimulated Brillouin scattering and stimulated Raman scattering on the system performance of OCDMA systems is presented. As some of the non-linearities may have correlated effects on the performance of the system, the relations between these effects are also investigated. Bit error rate results reveal that the most important unwanted effect was caused by FWM.

Triple-play services including video, voice and data demand service differentiation to provide end-users quality-of-service (QoS) requirements. Optical Code Division Multiple Access (OCMDA) systems have emerged as suitable solution to provide such QoS differentiation by varying the code weight. In this paper, the effect of choosing different code weight sets on the system capacity of a Variable-Weight OCDMA (VW-OCDMA) system deploying different detection techniques is investigated. Mathematical analysis is used to drive the Bit-Error Rate (BER) of active users in the system.

Whether signals mediated via growth factor receptors (GFRs) might influence lineage fate in multipotent progenitors (MPPs) is unclear. We explored this issue in a mouse knockin model of gain-of-function Flt3-ITD mutation because FLT3-ITDs are paradoxically restricted to acute myeloid leukemia even though Flt3 primarily promotes lymphoid development during normal hematopoiesis. When expressed in MPPs, Flt3-ITD collaborated with Runx1 mutation to induce high-penetrance aggressive leukemias that were exclusively of the myeloid phenotype. Flt3-ITDs preferentially expanded MPPs with reduced lymphoid and increased myeloid transcriptional priming while compromising early B and T lymphopoiesis. Flt3-ITD-induced myeloid lineage bias involved upregulation of the transcription factor Pu.1, which is a direct target gene of Stat3, an aberrantly activated target of Flt3-ITDs, further establishing how lineage bias can be inflicted on MPPs through aberrant GFR signaling. Collectively, these findings provide new insights into how oncogenic mutations might subvert the normal process of lineage commitment and dictate the phenotype of resulting malignancies.

Recently, Optical Code Division Multiple Access (OCDMA) systems are among the popular choice of research areas deployed in metro networks as they could provide service differentiation for different quality of signals in such networks. In OCDMA system Quality of Service (QoS) differentiation is realized by assigning dierent code weight or length for each user or service. In actual implementation which involves ber in the transmission, the ber impairment such as dispersion and nonlinear effects can greatly reduce the performance of the system, especially when the bit rate is high. In this thesis, mathematical and simulation model is proposed to analyze the performance of a Variable-Weight OCDMA (VW-OCDMA) system. The research was carried out by firstly developing a mathematical model for VWOCDMA system deploying Direct Detection (DD) and AND detection techniques. In the numerical analysis the effects of phase-induced intensity noise, shot noise and thermal noise was taken into account. Subsequently, different detection schemes i.e. DD and AND subtraction, as well as different optical sources i.e. broadband and laser were analyzed using software simulation. Three weights of 2, 4 and 6 were chosen for different services which represent voice, data and video. The simulationse tup was also used to investigate the effects of fiber impairments including chromatic dispersion, self-phase modulation and four wave mixing. Various dispersion compensation techniques were then applied in VW-OCDMA system. Finally,feasibility of the proposed system was investigated using practical experimentation to compare with the system’s performance in simulation environment. Three users with weight 6, 4 and 2 were used in experimental design, each transmitting data at rate of 1.25 Gbps. With reference to BER of 10−3, 10−9 and 10−12 for voice, data and video respectively, VW-OCDMA deploying DD scheme supports 95 users each operating at bit rate of 1.25 Gbps. Moreover, using non-zero dispersion s

A hybrid Spectral-Amplitude-Coding (SAC) - Optical Code Division Multiple Access (OCDMA) /Wavelength - Division-Multiple-Access (WDMA) using Random Diagonal (RD) code is proposed in this paper. The RD code is used in the proposed system due to its receiver's flexibility. The system is simulated using OptiSystem software. In our proposed system, four users of WDMA system with bit rate of 10Gbps is coupled with users of OCDMA system performing on bit rate of 1.25Gbps. Comparing to hybrid SAC-OCDMA /WDMA using KS code, the proposed system offers better performance in term of lower code length and lower bit error rate (BER) at the expense of higher number of filters. The result also shows that the BER of nine RD users are maintained at not more than 10-9 up to 75 km.

A hybrid Spectral-Amplitude-Coding (SAC) - Optical Code Division Multiple Access (OCDMA) /Wavelength - Division-Multiple-Access (WDMA) using Random Diagonal (RD) code is proposed in this paper. The RD code is used in the proposed system due to its receiver's flexibility. The system is simulated using OptiSystem software. In our proposed system, four users of WDMA system with bit rate of 10Gbps is coupled with users of OCDMA system performing on bit rate of 1.25Gbps. Comparing to hybrid SAC-OCDMA /WDMA using KS code, the proposed system offers better performance in term of lower code length and lower bit error rate (BER) at the expense of higher number of filters. The result also shows that the BER of nine RD users are maintained at not more than 10-9 up to 75 km.

The impact of Chromatic Dispersion (CD) and Non-Linear Effects (NLE) including Self-Phase Modulation (SPM) and Four-Wave Mixing (FWM), on the performance of a Variable-Weight Optical Code Division Multiple Access (VW-OCDMA) system at 1.25 Gbps is analyzed by simulation. The results show that CD is the most dominant effect, which increases the users bit error rate (BER) especially for the users with higher weights. In order to investigate the performance of system in service differentiation for users with different weights, Dispersion Compensating Fiber (DCF) is used to mitigate the effect of CD caused by Single Mode Fiber (SMF). The results show that users with higher weights have better performance as expected and impact of NLE is negligible for distance up to 150 km, considering low launched power.

This paper demonstrates the implementation of variable weight optical code division multiple access system in free space optics in order to support services with different quality of service requirement to the end users. This is achieved by varying the code weight of a particular user to provide signals with different quality level. Three users of different weights were transmitted at 622Mbps per channel rate over a free space optical channel. The received signals of different bit error rate of in several orders of magnitude such as 10-3, 10-9 and 10-12 are presented, to support the triple-play services, which are voice, data and video, respectively. The proposed system was simulated in different weather conditions with regard to Malaysia environment, whereby rain attenuations of 10 dB/km and 0.5 dB/km were used for heavy rain and clear weather, respectively.

This paper demonstrates the implementation of variable weight optical code division multiple access system in free space optics in order to support services with different quality of service requirement to the end users. This is achieved by varying the code weight of a particular user to provide signals with different quality level. Three users of different weights were transmitted at 622Mbps per channel rate over a free space optical channel. The received signals of different bit error rate of in several orders of magnitude such as 10-3, 10-9 and 10-12 are presented, to support the triple-play services, which are voice, data and video, respectively. The proposed system was simulated in different weather conditions with regard to Malaysia environment, whereby rain attenuations of 10 dB/km and 0.5 dB/km were used for heavy rain and clear weather, respectively.

The impact of Chromatic Dispersion (CD) and Non-Linear Effects (NLE) including Self-Phase Modulation (SPM) and Four-Wave Mixing (FWM), on the performance of a Variable-Weight Optical Code Division Multiple Access (VW-OCDMA) system at 1.25 Gbps is analyzed by simulation. The results show that CD is the most dominant effect, which increases the users bit error rate (BER) especially for the users with higher weights. In order to investigate the performance of system in service differentiation for users with different weights, Dispersion Compensating Fiber (DCF) is used to mitigate the effect of CD caused by Single Mode Fiber (SMF). The results show that users with higher weights have better performance as expected and impact of NLE is negligible for distance up to 150 km, considering low launched power.

Although several cytokineS have been demonstrated to be critical regulators of development of multiple blood cell lineages, it remains disputed to what degree they act through instructive or permissive mechanisms. Signaling through the FMS-like tyrosine kinase 3 (FLT3) receptor and the hematopoietin IL-7 receptor alpha (IL-7R alpha) has been demonstrated to be of critical importance for sustained thymopoiesis. Signaling triggered by IL-7 and thymic stromal lymphopoietin (TSLP) is dependent on IL-7R alpha, and both ligands adult mice doubly deficient in IL-7 and FLT3 ligand (FLT3L), TSLP does not play a key role in IL-7-independent or FLT3L-independent T lymphopoiesis. Furthermore, whereas previous studies implicated that the role of other cytokine tyrosine kinase receptors in T lymphopoiesis might not involve permissive actions, we demonstrate that ectopic expression of BCL2 is sufficient not only to partially correct the T-cell phenotype ofFIt3I(-/-) mice but also to rescue the virtually complete loss of all discernable stages of early T lymphopoiesis in FIt3I(-/-)II7r(-/-) mice. These findings implicate a permissive role of cytokine receptors of the hematopoietin and tyrosine kinase families in early T lymphopoiesis., QC 20120208

Although several cytokines have been demonstrated to be critical regulators of development of multiple blood cell lineages, it remains disputed to what degree they act through instructive or permissive mechanisms. Signaling through the FMS-like tyrosine kinase 3 (FLT3) receptor and the hematopoietin IL-7 receptor alpha (IL-7Ralpha) has been demonstrated to be of critical importance for sustained thymopoiesis. Signaling triggered by IL-7 and thymic stromal lymphopoietin (TSLP) is dependent on IL-7Ralpha, and both ligands have been implicated in T-cell development. However, we demonstrate that, whereas thymopoiesis is abolished in adult mice doubly deficient in IL-7 and FLT3 ligand (FLT3L), TSLP does not play a key role in IL-7-independent or FLT3L-independent T lymphopoiesis. Furthermore, whereas previous studies implicated that the role of other cytokine tyrosine kinase receptors in T lymphopoiesis might not involve permissive actions, we demonstrate that ectopic expression of BCL2 is sufficient not only to partially correct the T-cell phenotype of Flt3l(-/-) mice but also to rescue the virtually complete loss of all discernable stages of early T lymphopoiesis in Flt3l(-/-)Il7r(-/-) mice. These findings implicate a permissive role of cytokine receptors of the hematopoietin and tyrosine kinase families in early T lymphopoiesis.

Recent studies implicated the existence of adult lymphoid-primed multipotent progenitors (LMPPs) with little or no megakaryocyte-erythroid potential, questioning common myeloid and lymphoid progenitors as obligate intermediates in hematopoietic stem cell (HSC) lineage commitment. However, the existence of LMPPs remains contentious. Herein, global and single-cell analyses revealed a hierarchical organization of transcriptional lineage programs, with downregulation of megakaryocyte-erythroid genes from HSCs to LMPPs, sustained granulocyte-monocyte priming, and upregulation of common lymphoid (but not B and T cell-specific) genes. These biological and molecular relationships, implicating almost mutual exclusion of megakaryocyte-erythroid and lymphoid pathways, are established already in fetal hematopoiesis, as evidenced by existence of LMPPs in fetal liver. The identification of LMPPs and hierarchically ordered transcriptional activation and downregulation of distinct lineage programs is compatible with a model for HSC lineage commitment in which the probability for undergoing different lineage commitment fates changes gradually when progressing from HSCs to LMPPs.